Abstract

Background

Several recent studies reported aging effects on DNA methylation levels of individual
CpG dinucleotides. But it is not yet known whether aging-related consensus modules,
in the form of clusters of correlated CpG markers, can be found that are present in
multiple human tissues. Such a module could facilitate the understanding of aging
effects on multiple tissues.

Results

We therefore employed weighted correlation network analysis of 2,442 Illumina DNA
methylation arrays from brain and blood tissues, which enabled the identification
of an age-related co-methylation module. Module preservation analysis confirmed that
this module can also be found in diverse independent data sets. Biological evaluation
showed that module membership is associated with Polycomb group target occupancy counts,
CpG island status and autosomal chromosome location. Functional enrichment analysis
revealed that the aging-related consensus module comprises genes that are involved
in nervous system development, neuron differentiation and neurogenesis, and that it
contains promoter CpGs of genes known to be down-regulated in early Alzheimer's disease.
A comparison with a standard, non-module based meta-analysis revealed that selecting
CpGs based on module membership leads to significantly increased gene ontology enrichment,
thus demonstrating that studying aging effects via consensus network analysis enhances
the biological insights gained.

Conclusions

Overall, our analysis revealed a robustly defined age-related co-methylation module
that is present in multiple human tissues, including blood and brain. We conclude
that blood is a promising surrogate for brain tissue when studying the effects of
age on DNA methylation profiles.